Chromatin is a DNA-protein complex essential for eukaryotic cell differentiation and function. Its structure is maintained and regulated by a family of basic proteins, named histones. Histones are small proteins with molecular masses ranging from 11 kDa to 22 kDa. They are remarkably conserved in sequence and structure across species indicating their critical role in gene evolution. Five types of histones, termed H1, H2A, H2B, H3, and H4, exist in a variety of forms due to post-translational modifications of certain side chains. A striking common feature of histones is their high content of positively charged side chains, about one in four residues is either lysine or arginine. When a histone-DNA complex forms, the positive charges of the histone side chains neutralize the negative charges of chromosomal DNA. Specifically, H2A, H2B, H3, and H4 interact with repeats of 200 base pairs of chromosomal DNA to form nucleosomes. Then, H1 interacts with H2A to group the nucleosomes into second order structure. Higher-order structure of chromosomes involves the interaction of histones and chromosomal DNA with a series of nonhistone proteins.
H2B is an 125 or 126-residue heparin-binding histone. Sequence analysis shows homology of the amino-terminus of H2B with a heparin-binding lectin of human placenta and a heparin-binding peptide from a rat (hypercalcemic) Leydig cell tumor (Kohnke-Godt, B. et al. (1991) Biochemistry 30: 55-65; Rabbani, S. A. et al. (1992) Biochim. Biophys. Acta 1171: 229-230). Heparin is a negatively charged polysaccaride important in regulating various physiological processes. Heparin acts as an anticoagulant factor in hemagglutination, binds to growth factors such as pleiotrophin and midkine to regulate cell growth and differentiation, and functions as a component of proteoglycans, particularly in connective tissues and extracellular matrices.
The discovery of proteins related to a novel histone-like protein and polynucleotides which encode them satisfies a need in the art by providing new compositions useful in diagnosing, preventing, and treating disorders associated with cell proliferation.